We will continue to study the role of altered hemoglobin-oxygen binding in the adaptation to reductions in systemic arterial oxygen flow rate. We will continue to study patients in whom oxygen flow is reduced: anemic subjects, patients with arterial desaturation due to cyanotic congenital heart disease or respiratory disease, and patients with cardiac decompensation. The following questions will be examined in further detail: (1) What is the process leading to accumulation of red cell 2,3 DPG in response to reduced oxygen flow rate in human disease? (2) What is the extent of the ultimate hemoglobin-oxygen affinity change in vivo when 2,3 DPG rises in response to reduced oxygen flow? (3) What relative role do changes in blood flow, oxygen extraction and altered affinity play in the maintenance of oxygen utilization in low oxygen flow states? We will also continue to study in perfused skeletal and cardiac muscle in animals the following question: What is the physiological effect of an induced shift in the equilibrium binding of oxygen and hemoglobin on tissue oxygen delivery when other components of the delivery system, i.e., blood flow rate and arterial oxygen content, are controlled and limited?